This invention relates to a method for producing glycoside polymers or glycosides which are useful as materials for functional foods, biodegradable fibers, medicaments, and the like. More particularly, it relates to a method for producing glycoside polymers such as high molecular weight polysaccharides, polysaccharide-like polyesters or glycosides from natural resources such as glucose by using a solid superacid catalyst.
Synthetic fibers originated from petroleum such as polyamides (e.g. nylon) or polyesters are produced from petroleum originated in fossil, but such materials are limited resources and hence will be exhausted in future. By the way, some glycosides have an amino group (an alkaline functional group) and/or a carboxyl group (an acidic functional group) which are a functional group characteristic in such petroleum materials and hence may be useful as a material for producing fibers. However, it has never been succeeded to derive these glycosides into commercially usable fibers, except cellulose which is a polyacetal.
On the other hand, glycosides are extracted from sugarcare, coconut palm, prawn, crabs, sea tangle, woods, and the like, and hence those are unlimited resources and will be not exhausted forever. Besides, enzyme being capable decomposing glycosides are distributed widely in various organisms such as microorganisms, mammalia, etc., and hence, synthetic fibers produced by using these glycosides will probably be biodegradable. Accordingly, it will be much required to develop a method for producing synthetic fibers by using glycosides as the starting material.
The known methods for producing these synthetic fibers and starting materials therefor such as glycoside polymers or glycosides will roughly be classified into three methods, that is, a stepwise glycosylation method, a liquid polymerization method, and a bulk polymerization method.
As the stepwise glycosylation method, there has been used various Keonigs-Knorr""s glycosylation reactions for a long time (Chem.Rev.,93,1503(1993)) The stepwise glycosylation method comprises extending the chain of the glycoside molecules one-by-one. In this method, since glycosides are a polyfunctional molecule and have many hydroxy groups in the molecule, it is necessary to protect the most hydroxy groups other than the hydroxy group to be formed into glycoside bond, and only said hydroxy group to be reacted shall be remained without being protected in the reaction.
As the solution polymerization method, various methods are know, for example, a ring opening polymerization of anhydrous saccharides by Schuerch et al. (Adv. Carbohydr. Chem. Biochem., 39, 157 (1981)), a cyanoethylidene method by Kochetkov et al. (Tetrahedron, 43, 2389 (1987)), a method utilizing a reverse glycohydrolase by Kobayashi et al. (Adv. Polym. Sci., 121, 1 (1995)).
The ring opening polymerization can give high molecular weight stereoregular polysaccharides. However, since this method is an ion polymerization, the reaction shall be carried out under high vacuum condition. Besides, this method has to use a solvent such as dichloromethane which is harmful in view of environmental disruption.
The cyanoethylidene method can produce stereoregular polysaccharides having complicated structure, but it is problem in side-production of cyanides during the polymerization reaction, which are extremely toxic cyanic acid derivatives, such as potassium cyanide. Accordingly, this method is very dangerous.
Next, the method using an enzyme has been succeeded for production of cellulose, but it is difficult to obtain a high molecular weight product in high yield. Moreover, the enzyme to be used has a substrate specificity and hence, usable glycosides are very limited. So, this method is not generally available.
The final method, bulk polymerization method can form a glycoside bond by carrying the reaction without using solvent, wherein the glycosides are molten with heating and an acetal exchange reaction proceeds to form the glycoside bond. The bulk polymerization method of glucose, etc. by Richards et al. comprises melting a glycoside having unprotected hydroxy groups by heating at a high temperature and then subjecting to the polymerization in the presence of dichloroacetic acid catalyst (Carbohydr. Res., 208, 93 (1990)). However, this method still has a defect such as coloring of the product, and due to the side reaction, the product has less purity. Moreover, the catalyst used therein dissolves in the reaction system or in various solvents, and hence, it is difficult to remove the catalyst from the reaction mixture.
An object of the present invention is to prove an improved method for producing materials advantageous in view of keeping environment in good conditions, for example, materials useful for producing functional foods, biodegradable fibers, etc. by using glycosides which are unlimited resources in simple procedure and safety. Another object of the invention is to provide a method for producing polymers or glycosides by using glycosides having unprotected saccharide chains without a solvent or in an aqueous solvent in a simple step contrary to the conventional methods which require very complicated steps, and further, the catalyst used in the method is recycled.
The present inventors have found that when a glycoside is subjected to a melt polymerization or solution polymerization by using as a catalyst a specific solid superacid, the desired glycoside polymers can be produced in an extremely high yield, and further that when a glycoside is reacted with an alcohol in the presence of the solid superacid, the desired glycosides can easily be produced, and then the present invention has been accomplished.
The present invention relates to a method for producing glycoside polymers by subjecting a compound of the formula (1): 
wherein R1 is xe2x80x94OH, R2 is xe2x80x94OH or xe2x80x94NHCOCH3, R3 is xe2x80x94CH2OH, xe2x80x94COOH or xe2x80x94CH3, to a melt polymerization or solution polymerization in the presence of a solid superacid.
The starting compound of the formula (1) includes, for example, monosaccharides such as D-glucose, D-galactose, D-mannose (in the above formula (1), R1: xe2x80x94OH, R2: xe2x80x94OH, R3: xe2x80x94CH2OH), L-fucose (in the above formula (1), R1: xe2x80x94OH, R2: xe2x80x94OH, R3: xe2x80x94CH3), and the like, aldonic acids such as D-glucuronic acid, D-galacturonic acid (in the above formula (1), R1: xe2x80x94OH, R2: xe2x80x94OH, R3: xe2x80x94COOH), aminosugars such as N-acetyl-D-glucosamine, N-acetyl-D-galactosamine (in the above formula (1), R1: xe2x80x94OH, R2: NHCOCH3, R3: xe2x80x94CH2OH).
The solid superacids to be used as a catalyst include any conventional compounds which have hitherto been used as a catalyst in isomerization of alkyl group, or introduction of a keto group into aromatic hydrocarbons, for example, the following compounds:
SO44/ZrO2, SO4/SnO2, SO4/HfO2, SO4/TiO2, SO4/Al2O3, SO4/Fe2O3, SO4/SiO2, WO3/ZrO2, MoO3/ZrO2, WO3/SnO2, WO3/TiO2, WO3/Fe2O3, and B2O3/ZrO2 (cf K. Arata et al. J. Am. Chem. Soc., 101, 6439 (1979)) One or more of the above compounds are used. The amount thereof is not specified and is an amount effective for catalyzing the polymerization reaction, but it is usually in the range of 0.1 to 10 equivalent, preferably 1.0 equivalent to the starting compound (1).
Any commercially available solid superacids may be used as they stand, but those commercial products are sometimes wetted with atmospheric moisture, and hence, it is preferable to calcine the material by super-heating. For instance, the commercially available zirconia sulfate (SO4/ZrO2) is usually calcined at about 650xc2x0 C. for about 2 hours.
The melt polymerization and the solution polymerization can be carried out by conventional methods.
More particularly, it is carried out as follows.
When the compounds of the formula (1) have a melting point, for example, in case of D-glucose or D-glucuronic acid, they are subjected to a melt polymerization in the following manner to give the desired glycoside polymers.
A saccharide of the formula (1) is added to a chinal pot and thereto is added an equivalent amount of an activated solid superacid (e.g. zirconia sulfate) and is mixed. The mixture is reacted in an electric furnace without solvent at a temperature of a melting point of the compound (1) for 24 hours. After finishing the reaction, the reaction mixture is dissolved in a deionized water, the catalyst is removed by filtration with a filter paper or by centrifugation, and the filtrate is concentrated. The residue is purified by gel filtration with Sephadex-G25, and the filtrate is concentrated and then lyophilized to dry the product completely.
When the compounds of the formula (1) have no melting point, for example, N-acetyl-D-glucosamine, the product is prepared in the following manner.
A saccharide of the formula (1) having no melting point is added to a flask and thereto is added as a solvent a deionized water. To the mixture is added an equivalent amount of an activated solid superacid (e.g. zirconia sulfate) and the mixture is reacted with stirring at 100xc2x0 C. for 24 hours. The reaction mixture is dissolved in a deionized water, the catalyst is removed by filtration with a filter paper or by centrifugation, and the filtrate is concentrated. The residue is purified by gel filtration with Sephadex-G25, and the filtrate is concentrated and then lyophilized to dry the product safely.
When the starting compounds of the formula (1) is a monosaccharide or an amino sugar (in the formula (1), R3 is xe2x80x94CH2OH), the glycoside polymer produced by the present invention is a lycopolymer of the formula (2): 
wherein R1xe2x80x2 is xe2x80x94OH, R2xe2x80x2 is xe2x80x94OH or xe2x80x94NHCOCH3, and R3xe2x80x2 is xe2x80x94CH2OH, or any one or more of R1xe2x80x2, R2xe2x80x2 and R3xe2x80x2 is a residue of saccharide molecule of the formula (1), and j, k, l, and m means an absolute number of binding form of the saccharide molecules within the parentheses in the above formula, and j, k, l, mxe2x89xa70, provided that the total number of j, k, l, and m is in the range of 2 to 30. The binding form in the parentheses in the above formula means that the binding form in the parenthesis xe2x80x9cjxe2x80x9d is (1xe2x86x926)xe2x88x92xcex1 and xe2x88x92xcex2 bond, and the binding form in the parenthesis xe2x80x9ckxe2x80x9d is (1xe2x86x924)xe2x88x92xcex1 and xe2x88x92xcex2 bond, the binding form in the parenthesis xe2x80x9c1xe2x80x9d is (1xe2x86x923)xe2x88x92xcex1 and xe2x88x92xcex1 bond, and the binding form in the parenthesis xe2x80x9cmxe2x80x9d is (1xe2x86x922)xe2x88x92xcex1 and xe2x88x92xcex2 bond.
The starting compound of the formula (1) is fucose (in the formula (1), R3 is xe2x80x94CH3), the glycoside polymer obtained by the process is a glycopolymer of the above formula (2) wherein R3xe2x80x2 is xe2x80x94CH3, j=0, and other symbols R1, R2, k, l, and m are as defined above.
Further, when the starting compound of the formula (1) is an aldonic acid (in the formula (1), R2 is xe2x80x94OH, R3 is xe2x80x94COOH), the glycoside polymer produced by the present polymerization is a compound of the formula (3): 
wherein R1 is xe2x80x94OH, R2 is xe2x80x94OH, n is an integer of 2 to 30.
The present invention is further to provide a method for producing an amphiphilic compound of the formula (5): 
wherein R1 is xe2x80x94OH, R2 is xe2x80x94OH, R4 is as defined below, and R3 is xe2x80x94CH2OH or xe2x80x94CH3, which comprises reacting a monosaccharide of the formula (1) wherein R1 is xe2x80x94OH, R2 is xe2x80x94OH, R3 is xe2x80x94CH2OH or xe2x80x94CH3 (e.g. D-glucose, D-galactose, D-mannose, L-fucose, etc.) with a saturated or unsaturated alcohol of the formula (4):
R4xe2x80x94OHxe2x80x83xe2x80x83(4)
wherein R4 is an alkyl chain of the formula: xe2x80x94(CH2)pxe2x80x94CH3 (0xe2x89xa6pxe2x89xa623) or a corresponding unsaturated group having 1 to 2 unsaturated bonds, in the presence of a solid superacid as mentioned above.
The production of the formula (5) is specifically carried out in the following manner.
A monosaccharide of the formula (1) is entered in a flask and thereto is added an excess amount of a saturated or unsaturated alcohol of the formula (4) in the form of a solution. To the mixture is added an equiamount of an activated solid superacid (e.g. zirconia sulfate), and the mixture is stirred at 60-120xc2x0 C. for 24 hours. After the reaction is completed, the catalyst is removed by filtration with a filter paper using methanol or by centrifugation, the filtrate is concentrated. The concentrated mixture is passed through a silica gel column (chloroform) to remove unreacted alcohol (4), and then developed with a mixture of chloroform and methanol to purify and recover the desired compound (5).
The solid superacid used in the present method is recovered after the reaction, regenerated and is used repeatedly, which is economical.
The regeneration of the solid superacid is carried out as follows. The solid superacid is recovered from the filter or centrifuging tube after the desired product is separated from the reaction mixture, thereto is added 0.5 to 1N sulfuric acid and the mixture is suspended. After removing supernatant, to the remaining mixture is added a deionized water. The procedures of recovering, suspending and removing of the supernatant are repeated 2 to 3 times, and thereafter, the recovered product is calcined in an electric furnace at about 650xc2x0 C.